Grant: Project Grant

While previously underestimated, respiratory syncytial virus (RSV) contributes to a significant proportion of severe respiratory disease and mortality in the elderly, similar to influenza. With a growing elderly population, a RSV vaccine is urgently needed, but not available. The elderly tend to respond more weakly or inconsistently to vaccination unless they receive vaccines that are specifically developed for them. Our overall objective is to develop and characterize a RSV vaccine for elderly. As RSV infects the respiratory tract, the presence of virus neutralizing antibodies at this site is critical. Boosting and maintaining high neutralizing activity of antibodies in the serum by intramuscular vaccine administration may be adequate as serum antibodies can penetrate and protect the lower airways and lungs. However, mucosal immunization is required to induce production of local IgA antibody and the correct type of T lymphocytes in the respiratory tract. We already have a safe, effective vaccine candidate consisting of a protective antigen of RSV and an immunostimulatory adjuvant. When administered either intramuscularly or intranasally, this RSV vaccine induces long-term, protective immunity in several neonatal and adult animal models, e.g. mice, cotton rats and lambs. We have evidence that this vaccine also elicits an immune response in old mice. We will evaluate the magnitude and longevity of this immune response, as well as protection from RSV infection in old animals, and if necessary optimize the RSV vaccine. Furthermore, we will fully characterize the properties of this vaccine, which will expedite human clinical trials and licensing. An effective RSV vaccine will decrease morbidity and mortality due to RSV infection, which will in the future, improve the health of the elderly and significantly reduce health care costs. In addition, our new adjuvant has applications in vaccines against other respiratory pathogens such as influenza virus as well.